Numerous chemicals have been proposed for the purpose of controlling diseases in agricultural and horticultural crops. For example, a 3,4-dihydroisoquinoline derivative represented by general formula (1):
wherein R1 and R2 independently represent an optionally substituted alkyl group having 1 to 6 carbon atoms or R1 and R2 together with the carbon atom to which they are bound form an optionally substituted cycloalkyl group having 3 to 10 carbon atoms, X represents a halogen atom, optionally substituted alkyl group having 1 to 6 carbon atoms or optionally substituted alkoxy group having 1 to 6 carbon atoms, n represents an integer of 0 to 4, Y represents a halogen atom, optionally substituted alkyl group having 1 to 6 carbon atoms or optionally substituted alkoxy group having 1 to 6 carbon atoms, and m represents an integer of 0 to 4, is disclosed in Patent Document 1 as being useful as an agricultural and horticultural microbicide. Moreover, a group of compounds derived from a compound represented by general formula (1) are also effective as agricultural and horticultural microbicides, and these compounds can also be intermediates for the production of agricultural and horticultural microbicides (Patent Document Nos. 1 and 2). Consequently, being able to produce these compounds both simply and efficiently is an extremely important issue.
According to Patent Document 1, a compound represented by general formula (1) is disclosed as being able to be prepared by using a 3-cyanoquinoline derivative as a starting material and reacting with a phenethyl alcohol derivative or styrene derivative, thus demonstrating that a 3-cyanoquinoline derivative is an important raw material.
An examination of the prior art relating to 3-cyanoquinoline reveals that it is produced by methods such as: (I) a method in which 3-bromoquinoline and copper cyanide are reacted at 250° C. (Non-Patent Document 1), (II) a method in which 2-dimethoxymethylacrylonitrile and aniline are reacted followed by converting with aluminum chloride (Non-Patent Document 2), (III) a method in which 4-nitroquinoline-1-oxide and potassium cyanide are reacted followed by chlorinating with phosphorous oxychloride and further subjecting to catalytic hydrogenation using palladium as catalyst (Non-Patent Document 3) for conversion, (IV) a method in which 3-bromoquinoline, sodium cyanide, potassium iodide, copper iodide and dimethyl ethylenediamine are reacted for 24 hours in toluene for conversion (Patent Document 3), and (V) a method in which aniline and a sodium salt of 3,3-dimethoxy-2-formyl propionitrile are reacted in the presence of hydrochloric acid followed by converting to a substituted cyanoquinoline with p-toluenesulfonic acid (Non-Patent Document 4).
However, these methods have the problems indicated below. In the method of (I), in addition to requiring an extremely high reaction temperature of 250° C., copper cyanide is used, which is highly toxic and causes problems on disposal. In the method of (II), the total yield is only about 4%, thus indicating poor productivity. In the method of (III), in addition to using highly toxic potassium cyanide, catalytic hydrogenation using an expensive palladium catalyst only demonstrates a yield of about 56%. In the method of (IV), in addition to using transition metals that present problems on disposal and highly toxic sodium cyanide, the reaction time is long resulting in it being not an efficient method. In the method of (V), although the method per se is superior, the substituents on aniline are limited to strong electron donating groups such as a methoxy group. On the other hand, the reaction does not proceed not only in the case of aniline substituted with a fluorine atom or methyl group, but also in the case of unsubstituted aniline, thereby indicating that this method lacks versatility.
As can be understood from the above, since conventional production methods using 3-cyanoquinoline derivatives as starting materials have problems with respect to productivity of the 3-cyanoquinoline per se as well as only allowing the acquisition of 3-cyanoquinoline having a limited range of substituents, there has been a fervent desire for a method for efficiently producing 3,4-dihydroisoquinoline derivatives as an alternative to these methods.